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SAT0279 Cytokine Gene Polymorphisms (IL10, IL6, TNFα) in Children with Rheumatic Fever in Latvia
  1. V. Staņēviča1,
  2. L. Ņikitina-Zaķe2,
  3. L. Zepa2,
  4. Z. Dāvidsone1,
  5. R. Šantere3,
  6. A. Ščegolevs3
  1. 1Pediatrics, Riga Stradiņš University
  2. 2Latvian Biomedical Research and Study Centre
  3. 3Pediatrics, Children's Clinical University Hospital of Latvia, Riga, Latvia

Abstract

Background Rheumatic fever (RF) is an autoimmune disease which pathogenesis is based on the response of cellular and humoral immune system, that develops after Group A beta hemolytic Streptococci infection with following 45% obtained heart disease (Guilherme L, 2011). One of the most typical clinical manifestations is polyarthritis. So far it is found that genetic polymorphisms may affect the immune system functions and phenotype of RF clinical manifestations. Since cytokines are central immune system molecules, and cytokine gene promoter polymorphisms can affect cytokine production in vitro, the following polymorphisms are among the candidates to be studied in pathogenesis of rheumatic fever. The most frequently studied polymorphisms - TNFa-308G/A is associated with mitral valve (MV) damage and TNFa-238G/A - with myocarditis and aortal valve (AV) damage (Rajendranath R, 2007). Data are different and Hernandez-Pacheeco (2003) proved TNFa-238 as unrelated.

Objectives To investigate the following cytokine gene promoter polymorphisms – TNFa-238G/A (ra361525), -308G/A (rs1800795), IL 1-592C/A (rs1800872)-819T/C (rs1800871), -1082G/A (rs1800896) and IL6-174G/C (rs1800795) in patients with rheumatic fever in Latvia.

Methods Clinical and DNA material were analyzed of 70 rheumatic fever patients (born 1984–2002) and 254 healthy. Data and DNA from controls were obtained from the State Population Genome Database. To determine rs1800795 and rs1800896 polymorphisms, was used real time TaqMAn SNP genotyping. Other polymorphisms were analyzed performing polymorphism-containing region Sanger sequencing. Statistical analysis were done with Plink 1.06. All genotyped polymorphisms corresponded to Hardy-Weinberg equation and initial SNP genotyping efficiency was over 98.8%.

Results 48 out of 70 RF patients (68.5%) were boys, 22 (33.4%) were girls. Up to 7 years of age were 23 (32.8%) and after - 47 (67.1%) patients. Acquired rheumatic heart disease developed in 47 (67.1%) patients, MV insufficiency in 24 (34.3%) patients, AV insufficiency in 3 (4.3%) patients and combined MV and AV damage in 20 (28.6%) patients. Polyarthritis were diagnosed in 34 (48.6%) patients. 8 (11.4%) patients suffered from chorea minor and 3 (4.3%) patients had erythema annulare. Analyzing TNFa and IL-10 genes SNP of promoters in different clinical patients groups and comparing them with controls, statistically significant differences in the frequency of alleles were not observed, but in patients with polyarthritis IL-6 genes rs1800795 alleles showed statistically significant differences comparing with other clinical groups p=0.04737, OR=0.4621.

Conclusions 1. Inflammatory cytokine IL-6 gene promoter's-174G/C position (rs1800795) polymorphism is polyarthritis development affecting SNP in patients with rheumatic fever in Latvia. 2. There was no proven link between TNFa-238G/A and-308G/A SNP and acquired heart disease development.

Disclosure of Interest None declared

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